Regulation of male fertility by the bone-derived hormone osteocalcin

Traditionally, bone has been viewed as a relatively static tissue only fulfilling mechanical and scaffolding function. In the past decade however, this classical view of the bone has considerably evolved towards a more complex picture. It is now clear that the skeleton is not only a recipient for hormonal input but it is also an endocrine organ itself. Through the secretion of an osteoblast-derived molecule, osteocalcin, the skeleton regulates glucose homeostasis and male reproductive functions. When undercarboxylated, osteocalcin acts following its binding to a G-coupled receptor, Gprc6a, on pancreatic β cells to increase insulin secretion, on muscle and white adipose tissue to promote glucose homeostasis and on Leydig cells of the testis to favor testosterone biosynthesis. More recently, it was also shown that osteocalcin acts via a pancreas-bone-testis axis that regulates, independently of and in parallel to the hypothalamus–pituitary–testis axis, male reproductive functions by promoting testosterone biosynthesis. Lastly, in trying to expand the biological relevance of osteocalcin from mouse to human, it was shown that Gprc6a is a potential new susceptibility locus for primary testicular failure in humans. Altogether, these results shed new light on the importance of the endocrine role of the skeleton and also provide credence to the search for additional endocrine functions of this organ.     

Serum osteocalcin as an index of bone turnover in active rheumatoid arthritis and in active psoriatic arthritis

Summary Juxtaarticular osteoporosis is a recognized clinical feature in both rheumatoid arthritis (RA) and psoriatic arthritis (PA), while generalised osteopenia seems to be characteristic of RA only. To assess differences in bone turnover in the two forms of disease, we measured serum osteocalcin levels and other parameters of bone metabolism in two groups of female, ambulant, age-matched patients suffering from active RA or active PA and never treated with steroid therapy. Serum osteocalcin levels were significantly higher in RA patients than in PA patients (13.05±1.27 ng/ml vs 4.83±0.88 ng/ml;p<0.001), with a significant positive correlation between osteocalcin and serum alkaline phosphatase in both groups. These data suggest that bone turnover is higher in active RA than in active PA. Juxtaarticular osteoporosis could be mediated by local disease mechanisms both in RA and in PA, while factors specifically related to active RA seem to determine a more generalized impairment of bone turnover.     

生物材料表面固定粘附肽调节小鼠成骨细胞骨钙素的表达

目的：观察材料表面固定粘附肽RGD对小鼠成骨细胞骨钙素mRNA表达的影响。方法：采用自组装单层结构法含RGD的粘附肽PGDC共价结合在试件表面,建立RDGC和空白对照组。接种小鼠原代成骨细胞,分别收集培养第10,15,21天的细胞,提取总RNA,Northen印迹杂交法检测骨钙素mRNA的表达。结果：RGD组第15天即开始出现明显的骨钙素基因表达,对照组的基因表达出现在第21天。结论：材料表面固定RGD有促进骨钙素基因表达,影响小鼠成骨细胞分化的功能。     

Protective effect of ellagic acid on healing alveolar bone after tooth extraction in rat—A histological and immunohistochemical study

Objective

This study has attempted to evaluate the effects of ellagic acid (EA) on alveolar bone healing after tooth extraction in rats.

Design

Twenty-four Sprague Dawley (SD) male rats (200–250 g) were selected and were anaesthetised for the extraction of upper left incisor. Then, the rats were divided into two groups, comprising 12 rats each; the first group has been considered as a control group and was given only normal saline, whereas, the second group (treated group) was intragastrically administrated with EA daily once, for 28 days. Then three rats from each group had been selected on 7th, 14th, 21st, and 28th days to dissect their maxilla tissue either for histological observation and homogenisation purposes. The tissues fixed, decalcified and embedded in paraffin. Serial sections of 5 μm thickness were prepared and stained with haematoxylin and eosin (H&E) for the histological study. Similar sections were taken for immunohistochemical analysis to assess osteocalcin (OSC) and osteopontin (OPN). Furthermore, Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in homogenated gingival maxilla tissue of rat by commercial kit.

Results

Based on the histological analysis we have identified that, EA treatment has induced earlier trabecular bone deposition in the treated group, resulting in more organised bone matrix on the 14th, 21st, and 28th days after tooth extraction, as against the control group. In comparison to control group, the positive labelling of OSC and OPN of the treated group have been highly expressed in the alveolar socket on 14th, and 21st days, which has indicated a the possibility of formation of new bone trabeculae at the beginning of the mineralisation process, after tooth extraction. In the EA treatment group, lipid per-oxidation (MDA) was significantly decreased (P < 0.05), as opposed to the control group. However, the antioxidant defense enzyme (SOD) was significantly increased in the maxilla tissue treated with EA (P < 0.05), compared to control group, which suggests that, after tooth extraction, EA plays an important role in the protection against the induction of lipid per-oxidation, particularly after 28 days of treatment with EA.

Conclusion

This study has concluded that, EA may accelerated the healing process in teeth socket of rats. Furthermore, the EA treated group showed a stronger positive immunolabelling for OSC and OPN, when compared with the control group.     

糖皮质激素对肾小球疾病患者骨代谢影响因素的研究

目的　探讨长期应用糖皮质激素 (GC)治疗对肾小球疾病患者骨代谢影响的因素。方法　 2 0 7例肾小球疾病患者 ,应用常规剂量GC治疗 ,于治疗前及治疗后每隔 3～ 6个月 ,进行了 35 7例次腰椎和股骨近端骨密度 (BMD)、血钙、血磷和骨钙素浓度测定。结果　①用GC后骨钙素浓度明显降低 (P均 <0 0 0 5 ) ,但其不能预测BMD下降。②用药 15个月后男性各部位BMD均减少 (32 2～111 5 )mg/cm2 ,以L1 4和股骨粗隆更明显 (P均 <0 0 5 ) ,骨丢失率 3 3%～ 10 3% ;女性L1 4BMD均减少(4 3 8～ 76 0 )mg/cm2 ,以L1更明显 (P <0 0 5 ) ,骨丢失率 3 9%～ 7 9%。③年龄与各部位BMD变化呈负相关 ,但不影响GC造成的骨丢失。男性各部位、女性L1 4BMD减少与GC累计剂量和GC用药时间负相关。④用GC15个月 (GC累计剂量 10g以上 ) ,男性L1 4BMD正常的比例从 3/ 4至 3/ 5 ;女性L1和L2 BMD正常者从 3/ 4减少到 1/ 2。结论　长期口服糖皮激素导致与剂量和用药时间相关的腰椎和男性股骨粗隆骨丢失 ,年龄偏大和男性患者骨丢失更明显。     

Diurnal rhythm in serum osteocalcin: Relation with sleep,growth hormone,and PTH(1–84)

Summary We examined the role of sleep, growth hormone (GH), and parathyroid hormone [PTH(1–84)] as regulators of the diurnal rhythm of the osteoblastic bone marker, serum osteocalcin (OC). Nine normal subjects were followed with hourly blood sampling during one 24-hour period with norsleep deprivation. We found that the rhythm in serum OC did not exhibit significant changes (P>0.50). Serum OC (mean±SE) was 30.9±2.5 μg/liter during sleep (2330-0730 hours) versus 29.9±4.9 μg/liter during sleep deprivation (not significantly different). The serum GH rhythm was significantly different on the two occasions (P<0.01). A maximum GH peak (mean±SE) of 10.3±2.4 μg/liter occurred at 0136 hours±6 minutes during sleep compared with a maximal peak of 7.6±1.2 μg/liter (P<0.01) at 0245 hours ±20 minutes (P<0.01) during sleep deprivation. During sleep (2330-0730 hours), mean serum GH was 3.61±0.60 μg/liter compared with 2.39±0.40 μg/liter during sleep deprivation (P<0.005). Small insignificant changes occurred in serum PTH(1–84) and serum ionized calcium during the two occasions. We conclude that sleep and GH are not acute controlling factors of the diurnal rhythm in serum OC and the role of serum PTH(1–84) remains unsettled.     

Effect of warfarin on early rat tooth development

Summary Rat pups were treated from birth to 5 days of age with the vitamin K antagonist warfarin in order to investigate possible functions of the vitamin K-dependent dentin Gla protein (DGP) in tooth development. Warfarin completely eliminated the immunocytochemically detectable DGP which is a prominent feature of dentin in control rat pups, and also caused an increased concentration of DGP in odontoblasts. Warfarin treatment did not affect the ultrastructure of cells or the extracellular matrix in the tooth germs. The width of the predentin layer, which is considered to be correlated with the rate of mineralization, was unchanged. These results are the first to demonstrate that warfarin treatment prevents the accumulation of DGP in dentin, and that the deposition of DGP has no influence on the overall rate of dentin matrix mineralization in tooth germs.     

Vitamin K and Osteoporosis

Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it also exerts relevant effects on bone and the vascular system. In this review, we point out the relevance of an adequate vitamin K intake to obtain sufficient levels of carboxylated (active form) vitamin K dependent proteins (such as Osteocalcin and matrix Gla protein) to prevent bone health. Another bone-related action of Vitamin K is being a ligand of the nuclear steroid and xenobiotic receptor (SXR). We also discuss the recommended intake, deficiency, and assessment of vitamin K. Furthermore, we review the few available studies that have as pre-specified outcome bone fractures, indicating that we need more clinical studies to confirm that vitamin K is a potential therapeutic agent for bone fractures.     

丹参素对去势大鼠骨质量的影响

研究口服丹参素能否促进去势大鼠骨形成或减少骨丢失,从而提高骨质量。方法30只雌性SD大鼠随机分为三组,即空白对照组、模型对照组和丹参素组,每组10只。模型对照组和丹参素组行双侧卵巢切除术,其中,丹参素组采用丹参素灌胃（12.5 mg·kg ^-1·d ^-1）。90 d后处死所有大鼠,采用双能X线骨密度仪检测大鼠全身骨密度、股骨和腰椎骨骨密度,AG-IS型电子万能试验机检测股骨生物力学性能,ELISA法检测血清骨钙素和骨碱性磷酸酶（BALP）水平,HE染色后统计股骨近心干骺端成骨细胞数量。 结果与空白对照组比较,模型对照组骨密度、股骨生物力学指标、血清骨钙素和BALP水平均降低,骨组织中成骨细胞数量减少;而丹参素组全身骨密度、股骨和腰椎骨骨密度、股骨三点弯曲试验弹性模量、最大载荷、屈服强度、断裂点载荷、血清骨钙素和BALP水平及成骨细胞数量均高于模型对照组（ P＜0.05或 P＜0.01）。 结论丹参素可提高大鼠骨密度,增强大鼠生物力学性能,促进血清骨形成相关因子的表达以及增加成骨细胞数量,从而提高骨质量。     

216例老年男性骨代谢生化指标调查结果分析

目的调查老年男性血、尿中与骨吸收和骨形成有关的生化指标与年龄的关系,探讨老年男性骨质疏松症骨代谢生化指标的变化特点。方法分别应用高压液相色谱法、酶免疫分析法和电泳法测定２１６例老年男性血中骨钙素（ＢＧＰ）、Ⅰ型前胶原羧基肽（ＰＩＣＰ）、骨碱性磷酸酶和睾丸酮,尿中羟脯氨酸（Ｈｙｐ）、脱氧吡啶啉（Ｄｐｄ）和钙,与老年前期、青中年男性和绝经后女性比较。结果老年男性骨吸收指标随着年龄的增长而增高（Ｄｐｄ１２．６％,Ｈｙｐ２３．５％）,骨形成指标呈现随着年龄增长而降低的趋势（ＢＧＰ２２．２％,ＰＩＣＰ４５．９％）。两组指标均低于绝经后女性组和青中年男性对照组（Ｐ＜０．０１）。结论老年男性骨转化率低,而且具有骨吸收大于骨形成的特点